This review focuses on major causes and risk factors for death of patients with atrial fibrillation (AF). The authors analyzed current therapeutic strategies for managing patients with AF with respect of their effects on prediction and mortality. Special attention is paid to the strategy of rhythm control and the clinical significance of catheter ablation in the treatment of patients with AF and heart failure.

According to Russian epidemiological studies, the incidence of chronic heart failure (HF) in the general population is approximately 7%, increasing from 0.3% in the group aged 2029 years to 70% in patients aged 90 years [1]. In the general population, the incidence of atrial fibrillation (AF) ranges from 1% to 2%, which increases with age, that is, from 0.5% at the age of 4050 years to 5%15% at the age of 80 years [2]. HF and AF aggravate significantly each others course and mutually increase the risk of adverse outcomes [3, 4]. Moreover, the incidence of AF in patients with HF increases with increasing New York Heart Association (NYHA) grade; that is, among patients with HF of NYHA grade I, the incidence of AF is 5%, whereas among patients with HF NYHA grade IV, the AF incidence in 50% [5]. Chronic HF is a syndrome with complex pathophysiology, which is characterized by the activation of neurohumoral systems, namely, the reninangiotensinaldosterone system (RAAS), sympathetic nervous system (SNS), and insufficient activity of the natriuretic peptide (NUP) system. In the early stage of HF, i.e. asymptomatic dysfunction of the left ventricle, the activation of the SNS and RAAS plays a compensatory role aimed at maintaining cardiac output and circulatory homeostasis [6]. Moreover, the NUP system has a counter-regulatory function in relation to the RAAS and SNS, and with prolonged and excessive activation of the SNS and RAAS or with insufficient NUP system activity, imbalance occurs and HF progresses [7]. The brain natriuretic peptide (BNP) and biologically inactive N-terminal fragment of BNP (NT-proBNP) are the most studied and significant in clinical practice representatives of the NUP system. BNP and NT-proBNP are secreted by cardiomyocytes of the left ventricular (LV) myocardium in response to an increase in the mechanical load and stress of the LV myocardium. NT-proBNP is widely used as a test to rule out HF in patients with dyspnea. The NUP level also correlates with the severity and prognosis in patients with an established diagnosis of HF, and studies have reported that the NUP level acts as a criterion for treatment efficiency in patients with HF [8]. NT-proBNP is a biomarker not only for HF but also for several other conditions, such as acute coronary syndrome and myocardial infarction (MI), because it is associated with an increased risk of death from all causes, regardless of age, stable effort angina grade, myocardial infarction history, and LV ejection fraction (LVEF) [9]. NT-proBNP levels can be influenced by several additional factors such as age, obesity, or glomerular filtration rate. The prognostic value of NT-proBNP is relevant in comorbid patients with AF associated HF because AF can increase NT-proBNP levels independently [10]. Given that NUP secretion depends on intracardiac hemodynamics, the NT-proBNP levels may also depend on the approach to managing AF. Tachycardia is associated with high NT-proBNP levels [11]. The rhythm control approach has advantages over the heart rate control approach in patients with HF and LVEF 50% to reduce mortality and the number of unplanned hospitalizations due to HF progression [12]. To date, the prognostic significance of NT-proBNP levels in relation to the risk of adverse events in patients with HF and reduced LV systolic function associated with AF, depending on the approach of AF management, remains unresolved. This study aimed to assess the predictive value of NT-proBNP in relation to the development of adverse cardiovascular events in patients with permanent or persistent AF associated with HF and LVEF 50%.

Introduction. Brain natriuretic peptide (BNP) as marker of higher left ventricular myocardial mechanical stress has a strong prognostic value in patients with heart failure (HF). Elevated BNP levels are associated with the of malignant ventricular arrhythmias. Atrial fibrillation (AF) is known to futher elevate BNP levels and this can influence on BNP prognostic value. The aim of the study was to assess the predictive value of BNP in risk assessment of paroxysmal ventricular tachycardia (PVT) in patients with HF and AF. Materials and methods. Totally, 92 patients with sustained or persistent AF, HF with left ventricular ejection fraction < 50 %. All patients underwent transthoratic echocardiography; 24-hour ECG monitoring to assess the ventricular arrhythmia burden. BNP determination by enzyme immunoassay in venous blood serum. Results. Patients with HF, AF and PVTcompared with patients with HF and AF without PVT have higher levels of BNP (298,8 [149; 500,6] pg/ml versus 152 [145,7; 335,4] pg/ml, р = 0,02). There is a significant positive correlation between the level of BNP and the amount of PVT per 24 hours (r = 0,26; р < 0,05). Increased BNP levels are associated with an increased risk of VPT, OR = 3,71 [95 % CI 1,2 to 13,1]. Discussion. BNP is a novel biomarker to improve risk stratification of sudden cardiac death not only for patients in sinus rhythm but for patients with AF. Conclusions. BNP has a predictive value in risk assessment of PVT in patients with HF and AF.

Background. The variability in the activity of natriuretic peptides (NUPs) is determined genetically, as evidenced by the association of polymorphic variants encoding brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) with an increased risk of cardiovascular (CV) disease. The aim of the study. To determine the frequency of alleles and genotypes of the SNP rs989692 of the neprilysin gene (MME). To determine the association of SNP rs989692 in MME with the concentration of NUP and soluble neprilysin and to evaluate its prognostic value in relation to the development of adverse cardiovascular events in patients with heart failure (HF) associated with a left ventricular ejection fraction (LVEF) <50% and persistent or long-term persistent atrial fibrillation (AF). Material and methods. The main group included 152 patients with HF, the control group included 35 individuals without CV disease. The levels of ANP, BNP, NT-proBNP and soluble neprilysin were determined for all patients. The genetic study of the SNP rs989692 in the MME gene was carried out by polymerase chain reaction. The endpoint: hospitalization due to HF progression. The composite endpoint: hospitalization due to HF progression, new onset or progressive exertional angina pectoris, myocardial infarction. Results. The frequency distribution of genotypes and alleles of the SNP rs989692 in MME did not differ significantly between the control and experimental groups. The levels of ANP, BNP and neprilysin in patients with HF in combination with AF did not differ depending on the SNP rs989692 in MME genotype. Patients with HF associated with LVEF <50%, AF and TT genotype rs989692 in MME had higher levels of NT-proBNP (those with CC genotype – 964 [655.1; 1724] pg/ml, those with TC genotype – 1074.1 [857; 1944] pg/ml, those with the TT genotype – 2992 [886; 4885] pg/ml, p<0.05). The presence of the homozygous TT genotype in patients with HF combined with LVEF <50% and AF was associated with an increased risk of developing adverse CV events, OR=1.9 [95% CI from 1.2 to 3.09]. Conclusion. Patients with HF associated with LVEF <50% in combination with permanent or long-term persistent AF with homozygous TT genotype rs989692 of the MME gene have higher levels of NT-proBNP and a higher risk of developing adverse cardiovascular events.

Background. Increased levels of brain natriuretic peptide (BNP) and the N-terminal fragment of brain natriuretic peptide (NT-proBNP) in heart failure (HF) indicates atrial and ventricular myocardial remodeling. BNP and NT- proBNP have great prognostic value in patients with HF. However, atrial fibrillation (AF) can affect the interpretation of BNP and NT-proBNP. AF is one of the most common conditions in patients with HF and assessing the predictive value of BNP and NT-proBNP is extremely important in clinical practice for patients with HF and AF. Aim. To determine ventricular arrhythmias (VA) markers in patients with HF and AF. To estimate the predictive significance of BNP and NT-proBNP in the VA risk assessment in patients with HF and AF. Material and methods. Totally, 164 HF patients with left ventricular ejection fraction (LVEF <50%) were included into the study. All the patients underwent transthoracic echocardiography using standard echocardiographic positions; 24-hour ECG monitoring to assess types and nature of VA. BNP and NT-proBNP levels were determined by enzyme immunoassay (ELISA) in venous blood plasma. Results. In the group of patients with HF and AF paroxysms of non-sustained ventricular tachycardia (NSVT) were more frequently recorded compared to the patients with sinus rhythm (48 (52.2%) versus 21 (29.2%); p=0.005). Patients with HF and AF with NSVT compared with patients without NSVT have larger left atrial and left ventricular (LV) sizes and LV volumes; differences between LVEF being without statistical significance of the results. Patients with HF, AF and NSVT, compared with patients without NSVT, have significantly higher levels of BNP (298.8 [149; 500.6] pg/mL versus 152 [145.7; 335.4] pg/mL, p=0.02) and NT-proBNP (2071.5 [1385; 4652.4] pg/mL vs. 971 [778.5; 1452] pg/mL, p<0.0001). A significant positive correlation was found between the level of BNP and the amount of NSVT per day; there is a positive correlation between the level of NT-proBNP and the amount of NSVT per day. Conclusion. The incidence of NSVT among patients with HF and AF is higher compared with patients with HF and sinus rhythm. Patients with HF and AF with registered NSVT are characterized by larger LA and LV sizes and LV volumes compared to patients without NSVT. Increased concentrations of BNP and NT-proBNP have a prognostic value in risk assessment of VA in patients with HF and AF.